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SEL1L Expression Decreases Breast Tumor Cell Aggressiveness in Vivo and in Vitro¹

Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy [R. O., F. T., P. C., C. R., S. M.], and Istitute for Biomedical Technologies-CNR, 20090 Segrate, Milan, Italy [M. C., I. B.]

SEL1L, the human orthologue of the Caenorhabditis elegans sel-1 gene, is differentially expressed in breast primary tumors and in normal breast tissues. Analysis of a series of human primary breast carcinomas, using a monoclonal antibody raised against a SEL1L recombinant protein, revealed down-modulation or absence of SEL1L expression in about two-thirds of the tumors as compared with normal breast epithelial cells. Overall survival analysis of breast carcinoma patients indicated a statistically significant correlation between SEL1L down-modulation and poor prognosis. MCF-7, human breast carcinoma cells, were transfected with a construct containing the entire SEL1L cDNA driven by an inducible promoter and showed a dramatic reduction in anchorage-dependent growth and colony formation in soft agar. Growth of the transfected cells in Matrigel, an extracellular matrix rich with laminin, restored colony-formation ability. These results point to the role for SEL1L in breast tumor growth and aggressiveness, possibly involving cell-matrix interactions.

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